Clinical efficacy and safety of the BAT1706 (proposed bevacizumab biosimilar) compared with reference bevacizumab in patients with advanced nonsquamous NSCLC: A randomized, double-blind, phase III study.
Authors: Likun Chen, Dmytro Trukhin, Oleksii Kolesnik, Jose David David Gomez Rangel, Timucin Cil, Xingya Li, Irfan Cicin, Oleh Kobziev, Yihong Shen, Zhihua Liu, Ivashchuk Oleksandr, Ozgur Ozyilkan, Bondarenko Igor, Grygorii Ursol, Jun Chen, Kostiuk Oleksandr, Zhendong Chen, Helong Zhang, Deniz Tural, Li Zhang
Journal: Journal of Clinical Oncology (2022)

9041 Background: A Randomized, Double-blind, Phase III Study was conducted to confirm clinical similarity between BAT1706, a proposed biosimilar to reference bevacizumab, and EU-bevacizumab in patients with advanced non-squamous non-small cell lung cancer (NSCLC). Methods: Patients were randomized 1:1 to BAT1706 plus paclitaxel and carboplatin (Arm A) or EU-bevacizumab plus paclitaxel and carboplatin (Arm B) given three weeks for 6 cycles, followed by maintenance therapy with BAT1706 or EU- bevacizumab. The primary endpoint was overall response rate at Week 18 (ORR 18 ). Secondary endpoints included ORR at Week 6 and 12, best ORR, duration of response (DoR), progression-free survival (PFS), and overall survival (OS). Results: A total of 651 patients were randomized: BAT1706 (n = 325) or EU- bevacizumab (n = 326). In total, 649 randomized patients (BAT1706 (n = 325) or EU- bevacizumab (n = 324)) received at least one cycle of combination treatment. The median duration of therapy was 29.1 weeks (ranging from 3.0 to 62.1 weeks) in the Arm A and 27.0 weeks (ranging from 3.0 to 53.9 weeks) in the Arm B. The extent of exposure to BAT1706 and EU- bevacizumab was similar between these two arms. Overall, the proportion of patients achieving an ORR by Week 18 was comparable across Arm A and B (48.0% and 44.5%). The ORR risk ratio of 1.08 with 90% CI (0.94, 1.24) and the ORR risk difference of 0.03, with 95% CI (-0.04, 0.11) were within pre-specified equivalence margin. In addition, the multivariate-adjusted risk ratio was 1.07, with a 90% CI (0.93, 1.22). The ORR 18 risk difference between BAT1706 and EU- bevacizumab was 0.03, with the 2-sided 95% CI (-0.04, 0.11) that fell entirely within pre-specified equivalence margin. In addition, the multivariate-adjusted risk difference was 0.03, with a 95% CI (-0.04, 0.11). The hazard ratio stratified for time to PFS was 0.915 and the PFS rate at 12 months was 20.7% versus 21.8%. At the end of the study, there were no significant differences between both the treatments. The incidence of treatment-emergent adverse events (TEAEs) and study drug-related TEAEs was similar between these two arms. Overall, the safety profiles of BAT1706 were consistent with that of EU- bevacizumab, no new safety signals or noticeable trends were observed. The mean serum concentrations were comparable between BAT1706 and EU- bevacizumab over the entire sampling interval both in pre-dose and post-dose. The incidence of positive anti-drug antibodies results was low (≤5%) and decreased over time in both treatment arms. No patient was detected to have positive neutralizing anti-drug antibody result during the study. Conclusions: BAT1706 demonstrated clinical equivalence to reference EU-bevacizumab in terms of efficacy, safety, pharmacokinetics, and immunogenicity. Clinical trial information: NCT03329911.